British journal of clinical pharmacology最新文献

{"title":"Pharmacokinetics and pharmacodynamics of empagliflozin in paediatric patients aged 10-17 years with type 2 diabetes mellitus.","authors":"Juliane Rascher, Shen Cheng, Curtis Johnston, Sebastian Härtter, Wojtyniak Jan-Georg, Jan Marquard, Igor Tartakovsky, Lori M B Laffel","doi":"10.1002/bcp.70096","DOIUrl":"https://doi.org/10.1002/bcp.70096","url":null,"abstract":"<p><strong>Aims: </strong>To characterize the pharmacokinetics (PK) and PK/pharmacodynamics (PD) regarding glycosylated haemoglobin (HbA_1c) lowering using the paediatric data from DINAMO and to assess differences compared with adults.</p><p><strong>Methods: </strong>Population PK and PK/PD models previously developed for empagliflozin in adults and adolescents were re-estimated in a Bayesian framework. The PK model included 223 observations from 74 patients receiving empagliflozin 10 mg and 25 mg and the PK/PD model used 394 observations from 103 patients receiving empagliflozin (n = 52) or placebo (n = 51).</p><p><strong>Results: </strong>Empagliflozin PK was well described by a 2-compartment model with sequential zero-order and first-order absorption, with tested covariate effects of sex, age, race and estimated glomerular filtration rate on apparent clearance, and fixed allometric exponents on apparent clearance, apparent central volume of distribution, apparent intercompartmental clearance and apparent peripheral volume of distribution. Simulations of area under the curve at steady state (AUC_ss) demonstrated that adult and paediatric subjects exhibit similar AUC_ss. The PK/PD data were adequately described by a turnover model with disease progression and AUC_ss inhibiting the HbA_1c synthesis through an inhibitory maximum effect relationship. Simulations showed that the placebo-adjusted HbA_1c decrease at Week 26 in the paediatric population was larger than that in the adult population (-0.699 vs. -0.528%).</p><p><strong>Conclusion: </strong>A Bayesian estimation framework enabled the characterization of empagliflozin PK and PK/PD with a limited number of samples in paediatric patients aged 10-17 years. Overall, the results confirm 10 and 25 mg as the appropriate empagliflozin doses in paediatric patients aged 10-17 years with type 2 diabetes mellitus.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between ramelteon and 30-day mortality in ICU patients with COVID-19: A retrospective analysis of the MIMIC-IV database.","authors":"Yu Tian, Zai-Sheng Qin, Yun-Yang Han","doi":"10.1002/bcp.70099","DOIUrl":"https://doi.org/10.1002/bcp.70099","url":null,"abstract":"<p><strong>Aims: </strong>Melatonin may improve the prognosis of severe COVID-19 patients. However, the association between its analogue ramelteon and the survival outcomes of severe COVID-19 patients remains unclear. This retrospective study was conducted to investigate this knowledge gap.</p><p><strong>Methods: </strong>The data of COVID-19 patients admitted to the ICU were extracted from the Medical Information Mart for Intensive Care IV 3.0 database. Patients were categorized into the ramelteon group and the non-ramelteon group based on the corresponding treatment. The primary outcome was 30-day mortality. Subsequently, propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were employed to address confounding variables. Kaplan-Meier analysis, Cox proportional hazards regression and subgroup analyses were performed to evaluate the association between ramelteon exposure and survival outcomes.</p><p><strong>Results: </strong>This study included 607 unexposed patients and 459 exposed patients. Thirty-day mortality was 10.2% in the ramelteon group and 30.1% in the non-ramelteon group. Results from 301 patient pairs in the PSM cohort showed that ramelteon exposure was associated with significantly lower 30-day mortality (12.3% vs. 19.6%, P = 0.012). IPTW and Cox regression also supported this association (P < 0.05). Finally, subgroup analysis showed that invasive mechanically ventilated (IMV) patients on ramelteon may have a greater survival benefit (P interaction = 0.017).</p><p><strong>Conclusions: </strong>This study suggests an association between ramelteon exposure and lower 30-day mortality in ICU patients with COVID-19, particularly among those receiving IMV. However, given the retrospective design of this study, these findings should be interpreted as hypothesis-generating rather than definitive.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Randomized trial: Peppermint oil (menthol) pharmacokinetics in children and effects on gut motility in children with functional abdominal pain: 540 mg vs. 900 mg dose comparison.","authors":"Robert J Shulman, Bruno P Chumpitazi, Daniel Gonzalez, Uttam Garg, Salma Musaad, Jiali Wen, Gregory L Kearns","doi":"10.1002/bcp.70097","DOIUrl":"https://doi.org/10.1002/bcp.70097","url":null,"abstract":"<p><strong>Aims: </strong>There is a paucity of information on the pharmacokinetics (PK) and pharmacodynamics (PD) of menthol, the active ingredient in peppermint oil (PMO). We studied the PK of menthol (540 and 900 mg) in children and measured their effects on gut transit/contractility.</p><p><strong>Methods: </strong>Children 7-12 years of age with functional abdominal pain underwent wireless motility capsule (WMC) testing. One week later, they were randomized to 540 mg or 900 mg of oral enteric-coated PMO. Blood was sampled over 24 h to determine menthol PK. The WMC test was repeated while they took their respective dose (180 mg thrice or 180 mg five times daily) for a week.</p><p><strong>Results: </strong>Twenty-five children received 540 mg, and 15 received 900 mg (mean age 10.4 ± 1.1 years, 60% female). Peak plasma concentrations (C_max) were observed at approximately 2.5 h post-dose. There was no evident dose effect for the apparent elimination rate constant, time of peak plasma concentration (T_max), C_max, total plasma clearance, nor the apparent volume of distribution. Mean area under the plasma concentration vs. time curve (AUC) for the 900 mg PMO dose cohort was approximately 1.5-fold higher compared with the 540 mg dose; the difference disappeared correcting for dose. Colonic and whole bowel transit time were significantly positively correlated with menthol AUC. The 900 mg (vs. 540 mg) dose decreased colonic (P = 0.002) and whole gut (P = 0.02) contraction frequency.</p><p><strong>Conclusions: </strong>The PK of menthol derived from PMO demonstrates apparent dose-proportionality, and gut transit and contractility are associated with the systemic concentration of menthol.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sentinel dosing: A proposed algorithm to guide decision making on which cohorts in early phase clinical pharmacology trials should use this approach.","authors":"Jules A A C Heuberger, Perry de Jongh, Ewoud-Jan van Hoogdalem, Wim Tamminga, Pieter de Graeff, Geert Jan Groeneveld","doi":"10.1002/bcp.70090","DOIUrl":"https://doi.org/10.1002/bcp.70090","url":null,"abstract":"<p><strong>Aim: </strong>The aim of this paper is to describe a proposal for an algorithm to guide decision making on which cohorts in early phase pharmacology trials should employ a sentinel approach, thereby standardising and harmonising practices, and improving decision making around sentinel dosing. Sentinel dosing is an approach described in EMA guidelines; however, the guidance does not provide detail on which cohorts or dose levels sentinel dosing applies.</p><p><strong>Methods: </strong>This algorithm was designed using the expertise of senior scientific staff from the largest clinical research organisations in the Netherlands and after consultation with members of the ethics committee handling most early phase clinical drug trials in the Netherlands.</p><p><strong>Results: </strong>The algorithm describes a decision tree considering different aspects of the design of the trial, the IMP, and the prior knowledge of the IMP based on (pre)clinical data, to be used by investigators and regulators. Hereby the decision-making process on sentinel cohorts will be tailored to the specific IMP and information available. Starting in 2024, all three expert Phase 1 units that co-authored this paper are using the algorithm as guidance for decision-making on the implementation of sentinels in trials that are submitted to the EC Stichting BEBO.</p><p><strong>Conclusion: </strong>The algorithm provides further guidance and specification on when to implement sentinel dosing in early phase clinical trials, thereby creating a standardised and harmonised approach, which will improve the protection of subject safety and trial efficiency.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacology and relevant drug interactions of metamizole","authors":"David J. Brinkman,&nbsp;Linda C. Hendriksen,&nbsp;Irma M. Rigter,&nbsp;Markus W. Hollmann","doi":"10.1002/bcp.70101","DOIUrl":"10.1002/bcp.70101","url":null,"abstract":"<p>Metamizole is a frequently prescribed analgesic because of its favourable benefit/risk ratio compared with classic NSAIDs. However, increasing research shows that metamizole displays several drug interactions that are relevant to clinical practice. We reviewed the literature to summarize the pharmacology and most clinically relevant drug interactions of metamizole. Metamizole has a fast analgesic effect but a short half-life and duration of action. The exact mechanism of action of metamizole is currently not fully known. Studies showed that metamizole appears to be a moderate to strong inductor of the enzymes CYP3A4, CYP2B6 and CYP2C19; a weak inductor of CYP2C9; and a moderate inhibitor of CYP1A2. Furthermore, metamizole inhibits the effect of acetylsalicylic acid when taken simultaneously. Metamizole should be cautiously used together with other drugs that can cause agranulocytosis. If metamizole is prescribed in a high dosage (1000 mg three or four times daily) for more than 1 day, these pharmacokinetic and dynamic interactions should be taken into account.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 7","pages":"2095-2102"},"PeriodicalIF":3.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bcp.70101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic causal association between heart failure, frailty and poisoning by narcotics and psychodysleptics: A two-sample Mendelian randomization.","authors":"Bing Wang, Hong Yu, Meng Cai, Xianqiao Xie","doi":"10.1002/bcp.70091","DOIUrl":"https://doi.org/10.1002/bcp.70091","url":null,"abstract":"<p><strong>Aims: </strong>Observational studies have suggested associations between heart failure (HF), frailty and poisoning by narcotics and psychodysleptics (PNP). However, establishing causal relationships has been challenging. This study used a two-sample Mendelian randomization (MR) approach to investigate the genetically proxied causality between HF, frailty and PNP.</p><p><strong>Methods: </strong>Summary-level data from genome-wide association studies (GWAS) were utilized to investigate the causal relationship between frailty index (FI) and PNP risk, PNP and HF risk, as well as the bidirectional relationship between FI and HF. Various MR methods, including inverse-variance weighted (IVW), MR-Egger, weighted median and weighted mode, were employed. Horizontal pleiotropy, heterogeneities and the robustness of genetic variants were assessed using MR-Egger intercept tests, Cochran's Q test and leave-one-out analyses. The MR-PRESSO outlier test was applied to identify and remove outlier variants to mitigate potential pleiotropy.</p><p><strong>Results: </strong>Significant genetic causal associations were observed between FI and HF (IVW: OR = 1.42, 95% CI: 1.16-1.74) and between HF and FI (IVW: OR = 1.09, 95% CI: 1.05-1.14). However, no causal relationships were found between other variables. Sensitivity analyses demonstrated no evidence of horizontal pleiotropy or heterogeneity, confirming the robustness of the results.</p><p><strong>Conclusions: </strong>This MR study provides genetic evidence of a bidirectional causal relationship between FI and HF, highlighting the intertwined nature of frailty and heart failure. No genetically proxied causal associations were observed between FI and PNP or between PNP and HF. Further research, including age-stratified and longitudinal studies, is needed to validate these findings and explore the underlying mechanisms.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient, carer and healthcare professional perspectives on deprescribing in surgical wards: A mixed methods study.","authors":"Bonnie M Liu, Janani Thillainadesan, Aili Langford, Kenji Fujita, Danijela Gnjidic, Sarah N Hilmer","doi":"10.1002/bcp.70088","DOIUrl":"https://doi.org/10.1002/bcp.70088","url":null,"abstract":"<p><strong>Aims: </strong>The perspectives of patients and healthcare professionals regarding deprescribing in surgical wards within hospital settings are unknown. The aim of this study was to explore current practices, attitudes and the enablers and barriers to deprescribing in hospital for older surgical inpatients from the perspectives of doctors, pharmacists, patients and carers.</p><p><strong>Methods: </strong>A mixed methods study was performed. Two surveys were administered Australia-wide (revised Patients' Attitudes Towards Deprescribing questionnaire for patients/carers and Deprescribing Self-Efficacy Survey for doctors/pharmacists). Interviews, focus groups and observations of ward rounds were conducted with participants from five Australian hospitals. Quantitative data were analysed descriptively, while qualitative data were examined using a combined inductive and deductive approach, with results triangulated.</p><p><strong>Results: </strong>There were 109 survey participants (58 doctors/pharmacists and 51 patients/carers), 28 interview/focus group participants (15 doctors/pharmacists and 13 patients/carers) and eight ward round participants. Doctors and pharmacists reported low to moderate levels of confidence in deprescribing. While most patients and carers were satisfied with their medications, they expressed a willingness to consider deprescribing. Five themes were identified from the interviews, focus groups and ward round observations: (1) deprescribing is not a priority, (2) medication review occurs in response to triggers, (3) knowledge about deprescribing is limited, (4) deprescribing requires a team effort and (5) trust, rapport and communication are essential for successful deprescribing.</p><p><strong>Conclusions: </strong>Doctors working on surgical wards are unlikely to proactively deprescribe medications. A collaborative patient-centred approach involving geriatricians, clinical pharmacologists and pharmacists, along with educational interventions may facilitate deprescribing for surgical patients.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic-pharmacodynamic (PK/PD) modelling of cotadutide effect in patients with chronic kidney disease and type 2 diabetes mellitus.","authors":"Hongtao Yu, Victoria Parker, Viknesh Selvarajah, Lars Hansen, Darren Robertson, Bengt Hamrén, Anis Khan, Joanna Parkinson","doi":"10.1002/bcp.70093","DOIUrl":"https://doi.org/10.1002/bcp.70093","url":null,"abstract":"<p><strong>Aims: </strong>Cotadutide is a dual glucagon-like peptide-1/glucagon receptor agonist. The objective of the analysis was to develop a pharmacokinetic-pharmacodynamic (PK/PD) model to describe the relationship between cotadutide exposure and response on urine albumin-to-creatinine ratio (UACR), urinary albumin (UALB), and body weight in participants with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) using data from a Phase2b study (NCT04515849).</p><p><strong>Methods: </strong>A total of 247 participants with CKD and T2DM were randomized and titrated to either 100, 300 or 600 μg cotadutide, 1 mg semaglutide or placebo. UACR was measured biweekly from either morning void (Weeks 14 and 26) or spot urine (other visits). The analysis was implemented using a longitudinal non-linear mixed-effect model. The potential impact of covariates on efficacy in participants was quantified.</p><p><strong>Results: </strong>PK/PD models were developed, and a significant relationship was identified between cotadutide exposure and PD biomarkers of UACR, UALB and body weight. The models described the data adequately; greater changes in PD responses were observed with higher cotadutide doses. Baseline mean blood pressure and baseline UALB were found to affect the reductions in UACR and UALB, respectively. Model-predicted relative change from placebo in UACR, UALB and body weight after 26 weeks of 600 μg cotadutide treatment were -45.6% (-52.4%, -38.7%), -47.2% (-56.0%, -39.9%) and -5.3% (-7.6%, -4.1%), respectively.</p><p><strong>Conclusions: </strong>This modelling assessment was successfully applied for cotadutide to understand the relationship between cotadutide dosing regimen and the response in UACR, UALB and body weight. These models have general application in analysing and interpreting data from CKD/diabetic kidney disease (DKD) studies.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive analysis of adverse event profile changes with pertuzumab addition to trastuzumab-based breast cancer therapy: Disproportionality analysis using VigiBase.","authors":"Tatsuaki Takeda, Jun Matsumoto, Tomonori Sakai, Naohiro Iwata, Hirofumi Hamano, Toshihiro Koyama, Noritaka Ariyoshi, Yoshito Zamami","doi":"10.1002/bcp.70094","DOIUrl":"https://doi.org/10.1002/bcp.70094","url":null,"abstract":"<p><strong>Aims: </strong>Pertuzumab is used in combination with trastuzumab-based therapy for HER2-positive breast cancer. However, real-world safety information on pertuzumab remains limited. This study assessed the safety of adding pertuzumab to trastuzumab-based therapy for HER2-positive breast cancer using real-world data.</p><p><strong>Methods: </strong>VigiBase, the World Health Organization's global database of adverse events (AEs), containing reports from November 1967 to December 2023, was used. Signals for pertuzumab-associated AEs in breast cancer cases were detected using the reporting odds ratio (ROR).</p><p><strong>Results: </strong>Signals of trastuzumab plus pertuzumab relative to trastuzumab alone were detected in gastrointestinal disorders (ROR: 1.45, 95% confidence interval: 1.26-1.67), including diarrhoea (3.49, 2.83-4.30); infections and infestations (1.54, 1.24-1.91); and skin and subcutaneous tissue disorders (ROR: 1.63, 1.40-1.90), including pruritus (1.96, 1.51-2.55) and rash (1.63, 1.20-2.23). Further, signals of trastuzumab plus docetaxel plus pertuzumab relative to those of trastuzumab plus docetaxel were detected in gastrointestinal disorders (1.63, 1.38-1.93), including nausea (1.72, 1.24-2.39) and vomiting (1.48, 1.01-2.17), and in nervous system disorders (1.50, 1.20-1.87), including paraesthesia (2.60, 1.33-5.08) and peripheral sensory neuropathy (5.94, 1.79-19.71). The frequency of AEs causing or prolonging hospitalization was increased with trastuzumab plus pertuzumab compared to that with trastuzumab alone (1.18, 1.00-1.38).</p><p><strong>Conclusions: </strong>AE profiles after the addition of pertuzumab to trastuzumab-based therapy were comprehensively identified. The findings in this study highlight the importance of considering these AEs when selecting pertuzumab combination therapy to ensure the safety of patients with breast cancer.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From cradle to cane—(Dis)similarities between paediatric and geriatric clinical pharmacology: A commentary arising from the 2024 International Union of Basic and Clinical Pharmacology (IUPHAR) World Smart Medication Day","authors":"Karel Allegaert,&nbsp;Sarah N. Hilmer","doi":"10.1002/bcp.70092","DOIUrl":"10.1002/bcp.70092","url":null,"abstract":"&lt;p&gt;The International Union of Basic and Clinical Pharmacology (IUPHAR) initiated the World Smart Medication Day in 2021 to raise awareness on safer and more effective use of drugs. The IUPHAR World Smart Medication Day is specifically targeted at students and early career researchers, to help foster clinical pharmacology development. It has covered aspects related to drug safety, pandemics, pharmacogenomics and precision medicine and—most recently in 2024—clinical pharmacology at the extremes of age: &lt;i&gt;from cradle to cane&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;Ensuring safe and effective pharmacotherapy at the extremes of age requires a thorough understanding of pharmacokinetics and pharmacodynamics (PK/PD) alongside key covariates. Additionally, specific considerations for pharmacovigilance and clinical trial design are essential to address the unique challenges in these populations. The Paediatric and Geriatric Pharmacology Committees of the Clinical and Translational Section of the IUPHAR each created 5-min educational videos on the three topics, which we are accessible at no cost on the IUPHAR website (Paediatric|IUPHAR—International Union of Basic and Clinical Pharmacology and Geriatric|IUPHAR—International Union of Basic and Clinical Pharmacology). During an international webinar on World Smart Medication Day 2024 (World Smart Medication Day|IUPHAR—International Union of Basic and Clinical Pharmacology), the videos were presented, and issues for paediatric and geriatric clinical pharmacology were compared and contrasted. Awards were also presented for the international student poster competition on clinical pharmacology at the extremes of age.&lt;/p&gt;&lt;p&gt;In this commentary, we highlight (dis)similarities of clinical pharmacology challenges and approaches for paediatric and geriatric patient populations, presenting opportunities to learn from each other to improve safe and effective medication use for patients at both extremes of age.&lt;/p&gt;&lt;p&gt;When considering PK and PD, it is quite intuitive that additional reflections are warranted when considering either paediatrics or geriatrics, because population-specific characteristics are important factors to consider to attain effective and safe pharmacotherapy.&lt;/p&gt;&lt;p&gt;The extensive weight range (&lt;0.5 to &gt;50 kg, &gt;2 log value, even before considering obesity) within the paediatric field illustrates that extensive variability in both PK and PD should be anticipated. The main drivers hereby are maturational (age and weight), with a need for additional nuance in early infancy (postnatal, gestational or postmenstrual age, current &lt;i&gt;vs&lt;/i&gt;. birth weight). These drivers obviously display collinearity. Allometry or body surface area (weight &lt;i&gt;vs&lt;/i&gt;. size) is commonly considered to capture this collinearity, like the standard approach to report on glomerular filtration rate (mL/1.73m&lt;sup&gt;2&lt;/sup&gt;).&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;This ‘size’ mediated variability is further extended by non-maturational covariates, like pharmacogeneti","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 7","pages":"1881-1883"},"PeriodicalIF":3.1,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bcp.70092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}